scholarly journals Treatment Interruption and Regimen Change in Firstgeneration versus Second-generation Tyrosine Kinase Inhibitors used as First-line Therapy for Chronic Myeloid Leukemia

10.36469/9899 ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 181-191
Author(s):  
Melea A. Ward ◽  
Gang Fang ◽  
Gang Fang ◽  
Kristy L. Richards ◽  
Christine M. Walko
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Treatment Interruption ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Treatment Interruptions ◽  
Regimen Change

Background: Research has shown that treatment interruptions are associated with worse failure-free survival in chronic myeloid leukemia (CML); however they are commonly used in clinical trials to manage adverse events. Objectives: This study assessed the comparative rates of treatment interruption and regimen change between patients initiating first-line therapy with a first-generation tyrosine kinase inhibitor (1GTKI) imatinib versus second-generation TKI (2GTKI), dasatinib or nilotinib, for the treatment of CML in clinical practice. Methods: This was a retrospective cohort study using the Humana Research Database. Patients with CML who were between the ages of 18 and 89 and newly initiated 1GTKI or 2GTKI therapy between June 1, 2010 and December 31, 2011 were included. Treatment interruption and regimen change were compared using multivariable Cox proportional hazard regression models. Treatment interruption was defined as a gap in any TKI pharmacy claim that was longer than an allowable refill gap plus days’ supply from the previous TKI medication claim. Regimen change was defined as 1) a prescription claim for a different TKI therapy, or 2) increase in dose for the same medication. Results: 368 patients met the inclusion criteria: 1GTKI n=237, 2GTKI n=131. Patients initiating therapy with a 2GTKI had a 48% higher risk of treatment interruption versus patients initiating therapy with a 1GTKI (hazard ratio=1.48, 95% confidence interval 1.08-2.02). The time to treatment interruption was significantly longer in patients initiating therapy with a 1GTKI. Approximately 19% of patients had a regimen change, but there were no differences in rates of regimen changes between the two generations. Conclusions: In this study from a large single health plan population, treatment interruptions were more common among patients initiating therapy with a 2GTKI, yet regimen change rates did not vary by generation of TKI. Future research should assess reasons for treatment interruption and investigate these associations in other populations.

scholarly journals Nilotinib as the First Line Therapy in Managing Chronic Myelogenous Leukemia

e-CliniC ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 342
Author(s):  
Yuswanto Setyawan
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Myelogenous Leukemia ◽  
Newly Diagnosed ◽  
First Line ◽  
Hematopoietic Stem ◽  
First Line Therapy ◽  
Line Therapy ◽  
Imatinib Resistant

Abstrak: Leukemia mieloid kronis (chronic myeloid leukemia/CML) adalah penyakit klonal dari sel induk hematopoietik, secara sitogenetik ditandai dengan adanya kromosom Philadelphia (t[9,22][q34;q11]), yang merupakan fusi BCR-ABL1 onkogen. Nilotinib, generasi kedua inhibitor kinase tirosin, merupakan turunan aminopirimidin yang menghambat aktivitas kinase tirosin protein BCR-ABL. Dengan aktivitas penghambatan yang 10-60 kali lebih besar daripada imatinib, pada terapi lini pertama standar untuk CML, nilotinib efektif untuk CML fase kronik dan akselerasi yang resisten terhadap imatinib, namun terapi kombinasi nilotinib dengan agen lainnya masih diperlukan untuk pasien dengan CML krisis blas. Nilotinib aktif terhadap beberapa mutan BCR-ABL yang resisten terhadap imatinib, kecuali mutan T315I. Mutasi spesifik E255K/V, Y253H/F, F359C/V, dan L248V umumnya kurang sensitif terhadap nilotinib. Sebagai terapi lini pertama pada pasien CML fase kronik dengan Ph+ yang baru terdiagnosis, nilotinib menunjukkan CCyR dan MMR yang lebih tinggi serta pengembangan menjadi fase akselerasi/krisis blas serta resiko kematian yang lebih rendah, bila dibandingkan dengan imatinib. Simpulan penelitian ini ialah nilotinib lebih unggul dibandingkan dengan imatinib sebagai terapi lini pertama pada pasien CML fase kronik dengan Ph+ yang baru terdiagnosis,Kata kunci: chronic myeloid leukemia (CML), nilotinib, imatinib, terapi lini pertama  Abstract: Chronic myeloid leukemia (CML) is a clonal disease of the hematopoietic stem cells, cytogenetically characterized by Philadelphia chromosome (t[9,22][q34;q11]) leading to the fusion of BCR-ABL1 oncogene. Nilotinib, the second-generation tyrosine kinase inhibitor (TKI), is an aminopyrimidine derivative that inhibits the tyrosine kinase activity of the chimeric protein BCR-ABL. Its inhibitory activity is 10-60 times that of imatinib, therefore, as the standard first-line therapy for CML, nilotinib is effective in the case of CML-CP and CML-AP with imatinib resistant or intolerant. Albeit, novel approaches with nilotinib-based combinations are required for patients in CML-BP. Nilotinib is active against several imatinib-resistant BCR-ABL mutants with the exception of T315I. Specific mutations that are less sensitive to nilotinib include E255K/V, Y253H/F, F359C/V, and L248V. As the first-line therapy of patients with newly diagnosed Ph+ CML-CP, nilotinib has higher rates of CCyR and MMR, lower rates of progression to AP or BC, and lower risk of CML related death when compared with imatinib. In conclusion, nilotinib is superior to imatinib as the the first-line therapeutic option in newly diagnosed Ph+ CML-CP patients.Keywords: chronic myeloid leukemia (CML), nilotinib, imatinib, first line therapy

Medical decision analysis for first-line therapy of chronic myeloid leukemia

2014 ◽  
Vol 55 (8) ◽  
pp. 1758-1767 ◽  
Author(s):  
Ursula Rochau ◽  
Gaby Sroczynski ◽  
Dominik Wolf ◽  
Stefan Schmidt ◽  
Annette Conrads-Frank ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Decision Analysis ◽  
Myeloid Leukemia ◽  
Medical Decision ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Medical Decision Analysis

scholarly journals Clinical significance of dasatinib-induced pleural effusion in patients with de novo chronic myeloid leukemia

2018 ◽  
Vol 10 (3) ◽  
Author(s):  
Aya Nakaya ◽  
Shinya Fujita ◽  
Atsushi Satake ◽  
Takahisa Nakanishi ◽  
Yoshiko Azuma ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Clinical Features ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Late Onset ◽  
Molecular Response ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Treatment Agent

Dasatinib is currently approved for clinical use as a first-line treatment agent for newly diagnosed chronic myeloid leukemia (CML). However, only a few clinical trials have been performed to evaluate dasatinibinduced PE following first-line therapy. We investigated the incidence and clinical features of dasatinib-induced PE following first-line therapy in Japanese CML patients of real world clinical practice settings. Among 22 patients, the median age of PEpositive patients was higher than that of PEnegative patients. Major molecular response was achieved in 75% of PE-positive patients and 50% of PE-negative patients. Most patients developed PE more than 1 year after treatment. Appearance of PE is associated with better clinical response during dasatinib treatment, however it is developed at any time. Elderly and high-risk patients tend to develop PE. The clinical features of dasatinib-induced PE following first-line therapy might be late onset and might not immediately follow the increasing of large granular lymphocyte.

scholarly journals Nilotinib first-line therapy in patients with Philadelphia chromosome-negative/BCR-ABL-positive chronic myeloid leukemia in chronic phase: ENEST1st sub-analysis

2017 ◽  
Vol 143 (7) ◽  
pp. 1225-1233 ◽  
Author(s):  
Andreas Hochhaus ◽  
Franҫois-Xavier Mahon ◽  
Philipp le Coutre ◽  
Ljubomir Petrov ◽  
Jeroen J. W. M. Janssen ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy
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